Gouveia, Ricardo MGonzález-Andrades, ElenaCardona, Juan CGonzález-Gallardo, CarmenIonescu, Ana MGarzon, IngridAlaminos, MiguelGonzález-Andrades, MiguelConnon, Che J2017-04-062017-04-062017-03Gouveia RM, González-Andrades E, Cardona JC, González-Gallardo C, Ionescu AM, Garzon I, et al. Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability. Biomaterials. 2017 ; 121:205-2190142-9612http://hdl.handle.net/10668/2608Journal Article;Ideally, biomaterials designed to play specific physical and physiological roles in vivo should comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.enTissue templatingCorneal stromaSLATEsAnimalesAnisotropíaMateriales biocompatiblesColágenoCórneaSustancia propiaEpitelio anteriorMatriz extracelularEstudios de seguimientoHumanosInflamaciónElevaciónPéptidosConejosCélulas del EstromaMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Optical Phenomena::AnisotropyMedical Subject Headings::Chemicals and Drugs::Biomedical and Dental Materials::Biocompatible MaterialsMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::CollagenMedical Subject Headings::Anatomy::Sense Organs::Eye::Anterior Eye Segment::CorneaMedical Subject Headings::Anatomy::Sense Organs::Eye::Anterior Eye Segment::Cornea::Corneal StromaMedical Subject Headings::Anatomy::Sense Organs::Eye::Anterior Eye Segment::Cornea::Epithelium, CornealMedical Subject Headings::Anatomy::Cells::Cellular Structures::Extracellular Space::Extracellular MatrixMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up StudiesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Mechanical Phenomena::Mechanical Processes::LiftingMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::PeptidesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Lagomorpha::RabbitsMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::Stromal Cellsresearch article28092777open access10.1016/j.biomaterials.2016.12.0231878-5905PMC5267636